Method of fabricating an implantable medical device with biaxially oriented polymers

ABSTRACT

Methods and systems for manufacturing an implantable medical device, such as a stent, from a tube with desirable mechanical properties, such as improved circumferential strength and rigidity, are described herein. Improved circumferential strength and rigidity may be obtained by inducing molecular orientation in materials for use in manufacturing an implantable medical device. Methods of inducing circumferential molecular orientation by inducing circumferential flow in a molten polymer are disclosed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 12/806,785,filed Aug. 19, 2010, which is a divisional of application Ser. No.10/899,948, filed Jul. 26, 2004, now abandoned, each of which isincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to methods of fabricating implantable medicaldevices such as stents.

2. Description of the State of the Art

This invention relates to radially expandable endoprostheses which areadapted to be implanted in a bodily lumen. An “endoprosthesis”corresponds to an artificial implantable medical device that is placedinside the body. A “lumen” refers to a cavity of a tubular organ such asa blood vessel. A stent is an example of these endoprostheses. Stentsare generally cylindrically shaped devices which function to hold openand sometimes expand a segment of a blood vessel or other anatomicallumen such as urinary tracts and bile ducts. Stents are often used inthe treatment of atherosclerotic stenosis in blood vessels. “Stenosis”refers to a narrowing or constriction of the diameter of a bodilypassage or orifice. In such treatments, stents reinforce body vesselsand prevent restenosis following angioplasty in the vascular system.“Restenosis” refers to the reoccurrence of stenosis in a blood vessel orheart valve after it has been treated (as by balloon angioplasty orvalvuloplasty) with apparent success.

Stents have been made of many materials including metals and polymers.Polymer materials include both nonbioerodable and bioerodable plasticmaterials. The cylindrical structure of stents is typically composed ofa scaffolding that includes a pattern or network of interconnectingstructural elements or struts. The scaffolding can be formed from wires,tubes, or planar films of material rolled into a cylindrical shape. Inaddition, a medicated stent may be fabricated by coating the surface ofeither a metallic or polymeric scaffolding with a polymeric carrier. Thepolymeric carrier can include an active agent or drug. Furthermore, thepattern that makes up the stent allows the stent to be radiallyexpandable and longitudinally flexible. Longitudinal flexibilityfacilitates delivery of the stent and rigidity is needed to hold open abody lumen. The pattern should be designed to maintain the longitudinalflexibility and rigidity required of the stent. A stent should also haveadequate strength in the circumferential direction.

A number of techniques have been suggested for the fabrication of stentsfrom tubes and planar films or sheets. One such technique involves lasercutting or etching a pattern onto a material. Laser cutting may beperformed on a planar film of a material which is then rolled into atube. Alternatively, a desired pattern may be etched directly onto atube. Other techniques involve cutting a desired pattern into a sheet ora tube via chemical etching or electrical discharge machining. Lasercutting of stents has been described in a number of publicationsincluding U.S. Pat. No. 5,780,807 to Saunders, U.S. Pat. No. 5,922,005to Richter and U.S. Pat. No. 5,906,759 to Richter.

A treatment involving a stent involves both delivery and deployment ofthe stent. “Delivery” refers to introducing and transporting the stentthrough a bodily lumen to a region requiring treatment. “Deployment”corresponds to the expanding of the stent within the lumen at thetreatment region. Delivery and deployment of a stent are accomplished bypositioning the stent about one end of a catheter, inserting the end ofthe catheter through the skin into a bodily lumen, advancing thecatheter in the bodily lumen to a desired treatment location, expandingthe stent at the treatment location, and removing the catheter from thelumen. In the case of a balloon expandable stent, the stent is mountedabout a balloon disposed on the catheter. Mounting the stent typicallyinvolves compressing or crimping the stent onto the balloon. The stentis then expanded by inflating the balloon. The balloon may then bedeflated and the catheter withdrawn. In the case of a self-expandingstent, the stent may be secured to the catheter via a retractable sheathor a sock. When the stent is in a desired bodily location, the sheathmay be withdrawn allowing the stent to self-expand.

It is desirable for a stent to have certain mechanical properties tofacilitate delivery and deployment of a stent. For example, longitudinalflexibility is important for successful delivery of the stent. Inaddition, circumferential strength and rigidity and are vitalcharacteristics in deployment and for holding open a body lumen. Asindicated above, the pattern of the stent may be designed to providelongitudinal flexibility and rigidity.

However, the characteristics of the material of which a stent iscomposed also affects the mechanical properties of the stent. Anadvantage of stents fabricated from polymers is that they tend topossess greater flexibility than metal stents. Other potentialshortcomings of metal stents include adverse reactions from the body,nonbioerodability, and non-optimal drug-delivery. However, a potentialshortcoming of polymer stents compared to metal stents, is that polymerstents typically have less circumferential strength and rigidity.Inadequate circumferential strength potentially contributes torelatively high recoil of polymer stents after implantation intovessels. Furthermore, another potential problem with polymer stents isthat struts can crack during crimping, especially for brittle polymers.Therefore, methods of manufacturing polymer stents that improvecircumferential strength and rigidity are desirable. The embodiments ofthe present invention address the issue of improving circumferentialstrength and rigidity in polymer stents.

SUMMARY OF THE INVENTION

Various embodiments of the present invention include a method ofmanufacturing a stent, comprising: introducing a polymer into a formingapparatus comprising a first annular member disposed within a secondannular member, wherein the polymer is conveyed through an annularchamber as an annular film between the annular members; inducingcircumferential flow in the annular film; forming a tube from theannular film; and fabricating a scaffold comprising a plurality ofinterconnecting struts from the tube.

Further embodiments of the present invention include a method ofmanufacturing a stent, comprising: introducing a polymer into a formingapparatus comprising a first annular member disposed within a secondannular member, wherein the polymer is conveyed through an annularchamber as an annular film between the annular members; inducing spiralcircumferential molecular orientation in the annular polymer film with aspiral channel on at least a portion of a surface of the first annularmember or the second annular member; forming a tube from the annularfilm; and fabricating a scaffold comprising a plurality ofinterconnecting struts from the tube.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a tube.

FIG. 2 depicts a three-dimensional rendering of an implantable medicaldevice with a pattern.

FIG. 3 depicts a system and method of manufacturing an implantablemedical device.

FIG. 4A depicts a radial cross-section of a forming apparatus.

FIGS. 4B-7 depict an axial cross-section of a forming apparatus.

FIGS. 8A and 8B depict a method of expanding a tube.

FIG. 9 depicts an x-y coordinate plane.

FIG. 10A depicts a film.

FIG. 10B depicts a tube.

DETAILED DESCRIPTION OF THE INVENTION

For the purposes of the present invention, the following terms anddefinitions apply:

“Stress” refers to force per unit area, as in the force acting through asmall area within a plane. Stress can be divided into components, normaland parallel to the plane, called normal stress and shear stress,respectively. True stress denotes the stress where force and area aremeasured at the same time. Conventional stress, as applied to tensionand compression tests, is force divided by the original gauge length.

The term “elastic deformation” refers to deformation of an object inwhich the applied stress is small enough so that the object retains itsoriginal dimensions or essentially its original dimensions once thestress is released.

“Elastic limit” refers to the maximum stress that a material willwithstand without permanent deformation.

The term “plastic deformation” refers to permanent deformation thatoccurs in a material under stress after elastic limits have beenexceeded.

“Strength” refers to the maximum stress along an axis in testing which amaterial will withstand prior to fracture. The ultimate strength iscalculated from the maximum load applied during the test divided by theoriginal cross-sectional area.

“Modulus” may be defined as the ratio of the stress or force per unitarea applied to a material divided by the amount of strain resultingform the applied force.

“Strain” refers to the amount of elongation or compression that occursin a material at a given stress or load.

“Elongation” may be defined as the increase in length which occurs whensubjected to stress. It is typically expressed as a percentage of theoriginal length.

“Solvent” is defined as a substance capable of dissolving or dispersingone or more other substances or capable of at least partially dissolvingor dispersing the substance(s) to form a uniformly dispersed mixture atthe molecular- or ionic-size level. The solvent should be capable ofdissolving at least 0.1 mg of the polymer in 1 ml of the solvent, andmore narrowly 0.5 mg in 1 ml at ambient temperature and ambientpressure. A second fluid can act as a non-solvent for the impurity.“Non-solvent” is defined as a substance incapable of dissolving theother substance. The non-solvent should be capable of dissolving onlyless than 0.1 mg of the polymer in 1 ml of the non-solvent at ambienttemperature and ambient pressure, and more narrowly only less than 0.05mg in 1 ml at ambient temperature and ambient pressure.

Implantable medical device is intended to include self-expandablestents, balloon-expandable stents, stent-grafts, and grafts. Thestructural pattern of the device can be of virtually any design. Thedevice can also be made partially or completely from a biodegradable,bioabsorbable, or biostable polymer. The polymer may be purified toremove undesirable materials.

Polymers can be biostable, bioabsorbable, biodegradable or bioerodable.Biostable refers to polymers that are not biodegradable. The termsbiodegradable, bioabsorbable, and bioerodable are used interchangeablyand refer to polymers that are capable of being completely degradedand/or eroded when exposed to bodily fluids such as blood and can begradually resorbed, absorbed and/or eliminated by the body. Theprocesses of breaking down and eventual absorption and elimination ofthe polymer can be caused by, for example, hydrolysis, metabolicprocesses, bulk or surface erosion, and the like. If the material isused in coating applications, it is understood that after the process ofdegradation, erosion, absorption, and/or resorption has been completed,no polymer will remain on the device. In some embodiments, verynegligible traces or residue may be left behind. For stents made from abiodegradable polymer, the stent is intended to remain in the body for aduration of time until its intended function of, for example,maintaining vascular patency and/or drug delivery is accomplished.

Representative examples of polymers that may be used to fabricate animplantable medical device using the methods disclosed herein includepoly(N-acetylglucosamine) (Chitin), Chitoson, poly(hydroxyvalerate),poly(lactide-co-glycolide), poly(hydroxybutyrate),poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride,poly(glycolic acid), poly(glycolide), poly(L-lactic acid),poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide),poly(caprolactone), poly(trimethylene carbonate), polyethylene amide,polyethylene acrylate, poly(glycolic acid-co-trimethylene carbonate),co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules(such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid), polyurethanes, silicones, polyesters, polyolefins,polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymersand copolymers other than polyacrylates, vinyl halide polymers andcopolymers (such as polyvinyl chloride), polyvinyl ethers (such aspolyvinyl methyl ether), polyvinylidene halides (such as polyvinylidenechloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics(such as polystyrene), polyvinyl esters (such as polyvinyl acetate),acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides,polyethers, polyurethanes, rayon, rayon-triacetate, cellulose, celluloseacetate, cellulose butyrate, cellulose acetate butyrate, cellophane,cellulose nitrate, cellulose propionate, cellulose ethers, andcarboxymethyl cellulose. Additional representative examples of polymersthat may be especially well suited for use in fabricating an implantablemedical device according to the methods disclosed herein includeethylene vinyl alcohol copolymer (commonly known by the generic nameEVOH or by the trade name EVAL), poly(butyl methacrylate),poly(vinylidene fluoride-co-hexafluororpropene) (e.g., SOLEF 21508,available from Solvay Solexis PVDF, Thorofare, N.J.), polyvinylidenefluoride (otherwise known as KYNAR, available from ATOFINA Chemicals,Philadelphia, Pa.), ethylene-vinyl acetate copolymers, and polyethyleneglycol.

It is well known by those skilled in the art of polymer technology thatmechanical properties of a polymer may be modified by processes thatalter the molecular structure of the polymer. Polymers in the solidstate may be completely amorphous, partially crystalline, or almostcompletely crystalline. Crystalline regions in a polymer arecharacterized by alignment of polymer chains along the longitudinal orcovalent axis of the polymer chains. An oriented crystalline structuretends to have high strength and a high modulus (low elongation withapplied stress) along an axis of alignment of polymer chains. A highmodulus material tends to have a high degree of rigidity. Therefore, aregion of a polymeric material with a high degree of orientedcrystalline structure tends to have high strength and rigidity along anaxis of polymer chain alignment. Therefore, it may be desirable toincorporate processes that induce molecular orientation of polymerchains along a preferred axis or direction into manufacturing methods ofimplantable medical devices.

Furthermore, molecular orientation in a polymer may be induced, andhence mechanical properties modified, by applying stress to the polymer.The degree of molecular orientation induced with applied stress maydepend upon the temperature of the polymer. For example, below the glasstransition temperature, T_(g), of a polymer, polymer segments may nothave sufficient energy to move past one another. In general, molecularorientation may not be induced without sufficient segmental mobility.

The “glass transition temperature,” T_(g), is the temperature at whichthe amorphous domains of a polymer change from a brittle vitreous stateto a solid deformable state at atmospheric pressure. In other words, theT_(g) corresponds to the temperature where the onset of segmental motionin the chains of the polymer occurs. When an amorphous orsemicrystalline polymer is exposed to an increasing temperature, thecoefficient of expansion and the heat capacity of the polymer bothincrease as the temperature is raised, indicating increased molecularmotion. As the temperature is raised the actual molecular volume in thesample remains constant, and so a higher coefficient of expansion pointsto an increase in free volume associated with the system and thereforeincreased freedom for the molecules to move. The increasing heatcapacity corresponds to an increase in heat dissipation throughmovement. T_(g) of a given polymer can be dependent on the heating rateand can be influenced by the thermal history of the polymer.Furthermore, the chemical structure of the polymer heavily influencesthe glass transition by affecting mobility. Generally, flexiblemain-chain components lower the T_(g); bulky side-groups raise theT_(g); increasing the length of flexible side-groups lowers the T_(g);and increasing main-chain polarity increases the T_(g). Additionally,the presence of crosslinking polymeric components can increase theobserved T_(g) for a given polymer.

Above T_(g), molecular orientation may be readily induced with appliedstress since rotation of polymer chains, and hence segmental mobility,is possible. Between T_(g) and the melting temperature of the polymer,T_(m), rotational barriers exist, however, the barriers are not greatenough to substantially prevent segmental mobility. As the temperatureof a polymer is increase above T_(g), the energy barriers to rotationdecrease and segmental mobility of polymer chains tend to increase. As aresult, as the temperature increases, molecular orientation is moreeasily induced with applied stress.

Moreover, application of stress to a polymer between T_(g) and themelting temperature of the polymer, T_(m), may induce molecularorientation of the polymer, and hence, modify its mechanical properties.However, rearrangement of polymer chains may take place when a polymeris stressed in an elastic region and in a plastic region of the polymermaterial. A polymer stressed beyond its elastic limit to a plasticregion generally retains its stressed configuration and correspondinginduced molecular orientation when stress is removed. The polymer chainsmay become oriented in the direction of the applied stress which resultsin an oriented crystalline structure. The stressed polymer material mayhave a higher tensile strength in the direction of the applied stress.

Furthermore, as indicated above, a plastically deformed material tendsto retain its deformed configuration once the deforming stress isremoved. Stress applied to the material subsequent to the initialdeforming stress tends not to cause further deformation of the materialunless the applied stress is greater than the initial stress level thatcaused the deformation. Therefore, the behavior of a plasticallydeformed material may be more predictable within a range of stress. Thestress range may be less than the initial stress applied that caused theplastic deformation.

Additionally, application of heat with stress may facilitate deformationof a polymer under stress, and hence, modification of the mechanicalproperties of the polymer. A polymer deformed elastically with stressfacilitated with applied heat may retain induced molecular orientationby cooling the polymer before relaxing to an unstrained state.

Furthermore, above T_(m), a polymer exists as a polymer melt or in amolten state. In a polymer melt, there is a very small barrier to bondrotation, and hence, segmental mobility of polymer chains is very high.As suggested above, the higher the temperature, the greater thesegmental mobility, or generally, the more intense the molecular motion.Therefore, applying stress to a polymer melt may also induce molecularorientation. Stress may be applied to a polymer melt in the form of afilm as an isotropic stress or pressure which results in expansion ofthe film, as in a bubble. The expansion may result in circumferentialmolecular orientation in a direction of induced strain along the surfaceof the expanded film. Alternatively, a shear stress may be applied whichinduces flow in the polymer melt. The molecular orientation may tend tobe in the direction or along an axis of applied shear stress or flow.However, due to intense molecular motion, the induced molecularorientation is not stable. Once the shear stress is removed or the flowslows or stops, molecular motion may tend to dissipate the molecularorientation. The highest temperature at which molecular orientation isstable is less than or equal to the T_(m) of the polymer. Therefore, itmay be necessary to reduce the temperature of a polymer melt below T_(m)to inhibit or prevent dissipation of molecular orientation.

Various embodiments of methods for manufacturing an implantable medicaldevice with desirable mechanical properties are described herein. Someembodiments of manufacturing an implantable medical device may includefabricating the implantable medical device from a polymer conduit ortube. The tube may be cylindrical or substantially cylindrical in shape.For example, FIG. 1 depicts a tube 100. Tube 100 is a cylinder with anoutside diameter 110 and an inside diameter 120. FIG. 1 also depicts asurface 130 and a cylindrical axis 140 of tube 100. When referred tobelow, unless otherwise specified, the “diameter” of the tube refers tothe outside diameter of tube. In some embodiments, the diameter of thetube prior to fabrication of the implantable medical device may bebetween about 0.5 mm and about 3.0 mm. In other embodiments, thediameter of the tube prior to fabrication may be between about 1 mm and2 mm. An example of a tube prior to fabrication may include one with adiameter of 2.13 mm (0.084 in).

An implantable medical device may be fabricated from a polymer tube.Fabrication may include forming a pattern that includes at least oneinterconnecting element or strut on the tube. In some embodiments,forming a pattern on the tube may include laser cutting a pattern on thetube. Representative examples of lasers that may be used include anexcimer, carbon dioxide, and YAG. In other embodiments, chemical etchingmay be used to form a pattern on the tube. It is desirable to use alaser cutting technique which minimizes a size of a heat affected zone.A heat affected zone refers to a region of a target material affected bythe heat of the laser. Heat from the laser may tend to melt at least aportion of polymer in the heat affected zone. The molecular orientationinduced by applied stress may then be dissipated in the melted portion.The corresponding favorable change in mechanical properties may also bereduced or substantially eliminated. FIG. 2 depicts a three-dimensionalview of an implantable medical device 220 which may be formed from tube100 in FIG. 1.

FIG. 2 depicts an implantable medical device 150 that includes a patternof struts 160. The final etched out pattern should not be limited towhat has been illustrated as other stent patterns are easily applicablewith the method of the invention.

As discussed above, it is desirable for a polymer tube for use inmanufacturing an implantable medical device to have adequate strength inthe longitudinal direction, as shown by an arrow 135 in FIG. 1. Also,strength circumferential direction, as shown by an arrow 145 in FIG. 1,is also very important. A tube with biaxial molecular orientation, orequivalently, a tube with a desired degree of molecular orientation inboth the longitudinal and the circumferential directions may possess thedesirable mechanical properties. Implantable medical devices, such asstents, fabricated from tubes with biaxial orientation may possessmechanical properties similar to or better than metal stents with anacceptable wall thickness and strut width. Several embodiments ofmanufacturing implantable medical devices with biaxial orientation, andhence, with desired mechanical properties are described herein.

Polymer tubes may be formed by means of various types of formingmethods, including, but not limited to extrusion or injection molding.Alternatively, a polymer tube may be formed from sheets or films thatare rolled and bonded. In extrusion, a polymer melt is conveyed throughan extruder which is then formed into a tube. Extrusion tends to impartlarge forces on the molecules in the longitudinal direction of the tubedue to shear forces on the polymer melt. The shear forces arise fromforcing the polymer melt through a die and pulling and forming thepolymer melt into the small dimensions of a tube. As a result, polymertubes formed by conventional extrusion methods tend to possess asignificant degree of longitudinal orientation. However, conventionallyextruded tubes tend to possess no or substantially no orientation in thecircumferential direction.

Several embodiments of manufacturing implantable medical devices withbiaxial orientation may include the use of a forming apparatus, such asan extruder. Representative examples of forming apparatuses for thepresent invention may include single screw extruders, intermeshingco-rotating and counter-rotating twin-screw extruders and other multiplescrew masticating extruders.

Certain embodiments of manufacturing an implantable medical device witha forming apparatus may include radial expansion of an annular polymerfilm. In one embodiment, a method may include introducing a polymer intoa forming apparatus that includes a first annular member disposed withina second annular member. The first annular member may be a mandrel andthe second annular member may be a die. The polymer may be conveyedthrough an annular chamber as an annular film between the annularmembers. In some embodiments, the annular polymer film may be a polymermelt at a temperature above T_(m) of the polymer.

In one embodiment, the introduced polymer may be at a temperature abovea T_(m) of the polymer. Alternatively, the introduced polymer may be ata temperature below a T_(m) of the polymer. The forming apparatus may beconfigured to melt the polymer. In another embodiment, the polymer maybe introduced in a mixture that includes the polymer and a solvent. Asthe mixture is conveyed through the apparatus as an annular film, atleast some of the solvent may be vaporized and removed from theapparatus. Representative examples of solvents may include chloroform,acetone, chlorobenzene, ethyl acetate, 1,4-dioxane, ethylene dichloride,2-ethyhexanol, and combinations thereof.

Some embodiments may further include radially expanding the annularfilm. In one embodiment, the annular film may be expanded after exitingfrom the apparatus. In an embodiment, the annular film may be expandedwith a gas at a selected pressure. The gas may be conveyed through asecond annular chamber within the first annular member. A tube may thenbe formed from the expanded annular film. In an embodiment, the radialexpansion may induce circumferential orientation in the annular film,and hence in the resulting tube.

The method may further include fabricating an implantable medical devicefrom the tube. The fabricated device may have at least one mechanicalproperty more desirable than an equivalent device fabricated from anequivalent polymer tube formed from an annular film without radialexpansion. The dimensions of the polymer tube are equal to dimensions ofthe equivalent polymer tube formed from an annular film without radialexpansion. Additionally, the fabrication of the equivalent device fromthe equivalent polymer tube is the same as the fabrication of the devicefrom the polymer tube.

The induced molecular orientation may result in more desirablemechanical properties such as greater circumferential strength and/orgreater rigidity. In general, the radial expansion may be controlled toobtain a desired property of the implantable medical device. Forexample, the pressure of the gas and the temperature of the annular filminfluence the radial expansion.

In an embodiment, the expanded annular film may be drawn to a desireddiameter subsequent to radial expansion. In some embodiments, theannular film may be drawn by a puller. The puller may include a conveyorassembly that supports and sizes the annular film. The expanded annularfilm may be cooled during expansion and/or after drawing. For example,the annular film may be conveyed through a water bath at a selectedtemperature. Alternatively, the annular film may be cooled by air orsome other gas at a selected temperature.

As indicated above, it is desirable to cool the polymer melt to inhibitdissipation of the induced circumferential molecular orientation. In anembodiment, the cooling rate may be used to control the degree ofinduced molecular orientation in the polymer tube. The annular film maybe cooled at or near an ambient temperature, e.g. 25° C. Alternatively,the annular film may be cooled at a temperature below ambienttemperature.

In certain embodiments of the method, the gas used to expand the annularfilm may be conveyed through a second annular chamber within the firstannular member. The gas may be air or some other conveniently availablegas. The gas may be an inert gas such as argon, nitrogen, etc. Thepressure of the gas may be selected to expand the annular film to adesired inside diameter and outside diameter. For example, the flow ofthe gas may be configured to expand the annular film to an outerdiameter larger than the second annular member and an inner diameterlarger than the first annular member. In addition, the pressure of thegas may be controlled to obtain a desired property or a desiredimprovement of a property of the implantable medical device. Forexample, the greater the radial expansion, the more circumferentialmolecular orientation may be induced in the annular film. Furthermore,the drawing speed may also be controlled to obtain a desired degree ofinduced circumferential orientation. As the drawing speed is increased,the degree of induced circumferential orientation decreases.

It is desirable for the temperature of the annular film during expansionto be greater than the melting temperature of the polymer. As discussedabove, the higher the temperature, the greater the segmental mobility ofpolymer chains. Therefore, temperature may be used to control the degreeof molecular orientation in the annular film, and hence, to obtaindesired mechanical properties of the implantable medical device.

FIG. 3 illustrates an example of a system and method of manufacturing animplantable medical device that uses radial expansion to inducecircumferential molecular orientation. FIG. 3 depicts an axialcross-section of a portion of a forming apparatus 300. Forming apparatus300 includes a first annular member 310, a second annular member 320, afirst annular chamber 330, and a second annular chamber 340. Moltenpolymer in the form of an annular film 350 is conveyed through annularchamber 330 in the direction of arrows 360. A gas stream 370 at aselected pressure is conveyed through second annular chamber 340.Annular film 350 is exits from forming apparatus 300 to an expansionregion 380. Annular film 350 is radially expanded by gas 370 as it exitsforming apparatus 300. As shown, annular film 350 is expanded to adiameter greater than the outer diameter of first annular member 310 andthe inner diameter of the second annular member 320. Annular film 350 isthen drawn into a cooling region 390 to form a polymer tube 400. For thepurpose of comparison, FIG. 3 also depicts an annular film 410 formedwithout radial expansion. A polymer tube 420 formed from an annular film410 is also depicted.

Certain embodiments of manufacturing an implantable medical device witha forming apparatus may include inducing circumferential orientation byapplying shear stress to a polymer. An embodiment of a method formanufacturing an implantable medical device may include introducing apolymer into a forming apparatus with a first annular member disposedwithin a second annular member. The first annular member may be amandrel and the second annular member may be a die. The polymer may beconveyed through an annular chamber as an annular film between theannular members. In some embodiments, the annular polymer film may be apolymer melt at a temperature above a T_(m) of the polymer.

In one embodiment, the introduced polymer may be at a temperature abovea T_(m) of the polymer. Alternatively, the introduced polymer may be ata temperature below a T_(m) of the polymer. The forming apparatus may beconfigured to melt the polymer. In another embodiment, the polymer maybe introduced in a mixture that includes the polymer and a solvent. Asthe mixture is conveyed through the apparatus as an annular film, atleast some of the solvent may be vaporized and removed from theapparatus.

In some embodiments, the method may further include inducingcircumferential flow in the annular film. A polymer tube may be formedfrom the annular film. It is advantageous for the temperature of theannular film to be greater than the melting temperature of the polymer.The annular film may be removed from the forming apparatus.

In an embodiment, the induced circumferential flow may inducecircumferential orientation in the annular film, and hence in theresulting polymer tube. Some embodiments may then include fabricating animplantable medical device from the polymer tube.

In certain embodiments, a mechanical property of the device may be moredesirable than a mechanical property of an equivalent device formed froma polymer tube formed from an annular polymer film formed withoutcircumferential flow. The dimensions of the polymer tube are equal todimensions of the equivalent polymer tube formed from an annular polymerfilm formed without circumferential flow. Additionally, fabrication ofthe equivalent device from the equivalent polymer tube is the same asthe fabrication of the device from the polymer tube. The inducedmolecular orientation may result in more desirable mechanical propertiessuch as greater circumferential strength and/or greater modulus orrigidity. In general, the circumferential flow may be controlled toobtain a desired property of the implantable medical device.

In an embodiment, the annular film subjected to circumferential flow maybe drawn to a desired diameter. The annular film may also be cooledduring expansion and/or after drawing in the manner described above.

Various embodiments of a method of inducing circumferential orientationmay be distinguished by the manner of inducing circumferential flow.Several embodiments may include inducing circumferential flow in theannular film by rotating the first annular member, the second annularmember, or both annular members. It is expected that counter-rotation ofboth the first annular member and the second annular member may inducethe greatest shear on the annular film, and hence, induce the greatestcircumferential orientation. In some embodiments, the degree of inducedorientation may be controlled by parameters such as the rotation speedand relative rotation speed of the annular members.

In certain embodiments, circumferential flow may be induced by a spiralchannel on at least a portion of a surface of the rotating first annularmember and/or the rotating second annular member. The spiral channel maytend to induce spiral circumferential molecular orientation in theannular polymer film.

Moreover, drawing the annular film may influence the inducedcircumferential molecular orientation. Typically, the annular polymerfilm is exposed to air at ambient temperature while it is being drawn.As a result, the annular film tends to cool as it is drawn. The coolingmay cause dissipation in molecular orientation in the annular film.Therefore, the length of a drawing region may be directly proportionalto a cooling rate of an annular film, and hence, the dissipation ofmolecular orientation. The rotational speed of annular member(s) maycompensate for the dissipation in molecular orientation due to cooling.However, the rotational speed of annular members(s) is limited since theannular members may become unstable at sufficiently high rotationspeeds.

FIGS. 4A and 4B illustrate an example of a system and method ofmanufacturing an implantable medical device that uses circumferentialflow to induce molecular orientation. FIG. 4A includes a radialcross-section of a forming apparatus 500 and FIG. 4B includes an axialcross-section of a portion of forming apparatus 500. Forming apparatus500 includes a first annular member 510, a second annular member 520, afirst annular chamber 530, and a second annular chamber 540. As depictedby FIG. 4A, first annular member 510 and second annular member 520 areconfigured to rotate as depicted by arrows 515 and 525, respectively.FIG. 4B shows that molten polymer in the form of an annular film 550 isconveyed through annular chamber 530 in the direction of arrows 560.Rotation of first annular member 510 and/or second annular member 520induce circumferential flow in annular film 550. Annular film 550 isremoved from forming apparatus 500 to a drawing region 580. As shown,annular film 550 is drawn to a desired diameter smaller than thediameter of second annular member 520. Annular film 550 is then drawninto a cooling region 590 to form a polymer tube 595.

In another embodiment, circumferential flow may be induced in theannular film with at least a portion of the annular film external to theapparatus. The annular film external to the apparatus may be positionedover or within a third annular member. The third annular member may beconfigured to rotate at least a portion of the annular film externalapparatus. In an embodiment, the annular film may exit the formingapparatus and be drawn over or within the third annular member beingformed into the polymer tube. The rotating portion of the annular filmmay induce circumferential flow, and hence, circumferential molecularorientation in the annular film from at least a point of exit from theforming apparatus to the rotating third annular member. The degree ofinduced orientation may be controlled by the rotation speed of the thirdannular member.

In certain embodiments, circumferential flow may be induced in at leasta portion of the annular film external to the apparatus with at least aportion of the first annular member that is external to the apparatus.Rotation of the first annular member induces circumferential flow to atleast a portion of the annular film external to the apparatus.

FIG. 5 illustrates another example of a system and method with inducedcircumferential flow similar to the system and method depicted in FIGS.4A and 4B. FIG. 5 also depicts an axial cross-section of a portion of aforming apparatus 600, similar to forming apparatus 500 in FIGS. 4A and4B. However, the system in FIG. 5 further includes a third annularmember 685. An annular film 650 is exits from forming apparatus 600 to adrawing region 680 Annular film 650 is then positioned within thirdannular member 685. Third annular member 685 is configured to rotate, asshown by an arrow 687. Rotation of third annular member 685 inducescircumferential flow on the portion of annular film 650 positioned onthird annular member 685. Rotation of the portion of annular film 650induces circumferential flow on the portion of annular film 650 at leastin drawing region 680. As shown in FIG. 5, annular film 650 is drawnfurther into a cooling region 690 to form a polymer tube 695. Firstannular member 610 and/or second annular member 620 may also beconfigured to rotate. Rotation of first annular member 610 and/or secondannular member 620 may induce circumferential flow in annular film 650within forming apparatus 600.

FIG. 6 illustrates another example of a system and method with inducedcircumferential flow similar to the system and method depicted in FIG.5. FIG. 6 also depicts an axial cross-section of a portion of a formingapparatus 700, similar to forming apparatus 600 in FIG. 5. However, thesystem in FIG. 5 includes a first annular member 710 that extendsaxially external to forming apparatus 700. An annular film 750 is exitsfrom forming apparatus 700 to a drawing region 780. Annular film 750 isthen positioned within a third annular member 785. Third annular member785 is configured to rotate, as shown by an arrow 787. Rotation of thirdannular member 785 induces circumferential flow on the portion ofannular film 750 positioned on third annular member 785. Rotation of theportion of annular film 750 induces circumferential flow on the portionof annular film 750 at least in a drawing region 780. As shown in FIG.6, annular film 750 is drawn further into a cooling region 790 to formpolymer tube 795. First annular member 710 and/or second annular member720 may also be configured to rotate. Rotation of first annular member710 may induce circumferential flow in annular film 750 within formingapparatus 700 and within drawing region 780. Rotation of annular member720 may induce circumferential flow in annular film 750 within formingapparatus 700.

In a further embodiment, circumferential flow in the annular film may beinduced by rotating the polymer tube. The polymer tube may be rotated bypositioning the polymer tube over or within a third annular member thatis configured to rotate the polymer tube. The annular film may be cooledto form the polymer tube. The rotating polymer tube may inducecircumferential flow, and hence, circumferential orientation in theannular film from the polymer tube to at least the point of exit of theannular film from the apparatus.

FIG. 7 illustrates another example of a system and method with inducedcircumferential flow similar to the system and method depicted in FIGS.4-6. FIG. 7 also depicts an axial cross-section of a portion of aforming apparatus 800, similar, for example, to forming apparatus 500 inFIG. 4B. However, the system in FIG. 7 includes a fourth annular member805. An annular film 850 is exits from forming apparatus 800 to adrawing region 880. As shown in FIG. 7, annular film 850 is drawn into acooling region 890 to form a polymer tube 895. Polymer tube 895 ispositioned on fourth annular member 805. Fourth annular member 805 isconfigured to rotate, as shown by an arrow 807. Rotation of fourthannular member 805 rotates polymer tube 895 which inducescircumferential flow on the portion of annular film 850 at least indrawing region 880. First annular member 810 and/or second annularmember 820 may also be configured to rotate to induce circumferentialflow.

Furthermore, some embodiments that include inducing circumferentialorientation in a method of manufacturing implantable medical devices mayinclude application of stress to a polymer at temperatures less than orequal to a T_(m) of the polymer. For example, circumferential molecularorientation in a polymer tube may be induced after fabrication of atube.

Certain embodiments of a method of manufacturing an implantable medicaldevice may include radially expanding a tube about a cylindrical axis ofthe tube from a first diameter to a second diameter. Some embodimentsmay include expanding a polymer tube plastically beyond the yield pointor elastic limit of the polymer. The radial expansion of the polymertube may induce circumferential molecular orientation, and hence,desired circumferential strength and modulus or rigidity in the polymertube. As indicated above, a polymer expanded beyond its yield pointtends to retain its expanded configuration, and hence, tends to retainthe induced molecular orientation. An implantable medical device maythen be fabricated from the expanded tube having a second diameter whichis greater than the first diameter. An implantable medical device maythen be fabricated from the expanded tube having a second diametergreater than the first diameter.

In certain embodiments, the tube may be expanded radially by applicationof radial pressure. It may be desirable apply a pressure less than aboutan ultimate stress of the polymer to inhibit or prevent damage to thetube. In some embodiments, radial pressure may be applied to the polymertube by positioning the tube within an annular member and conveying agas at a selected pressure into a proximal end of the polymer tube. Adistal end of the polymer tube may be closed. The end may be open insubsequent manufacturing steps. The annular member may act to controlthe diameter of the expanded tube by limiting the expansion to theinside diameter of the annular member. The insider diameter of theannular member may correspond to a desired diameter of the tube.Alternatively, the pressure of the conveyed gas may be used to controlthe expansion of the tube to a desired diameter.

Some embodiments may include applying heat to the tube to facilitateradial expansion of the tube. In some embodiments, the tube may beheated prior to, contemporaneously with, and/or subsequent to applyingradial pressure to the tube. In one embodiment, the tube may be heatedby conveying a gas at a temperature greater than an ambient temperatureon and/or into the tube.

Some embodiments may include cooling the expanded tube prior tofabrication of the medical device. The expanded tube may be cooled at atemperature below an ambient temperature. Alternatively, cooling theexpanded polymer tube may include cooling the expanded polymer tube at atemperature at or near an ambient temperature.

In an embodiment, the device may include at least one mechanicalproperty more desirable than an equivalent device fabricated from anequivalent polymer tube formed without radial expansion. The dimensionsof the expanded polymer tube are equal to dimensions of the equivalentpolymer tube formed without radial expansion. In addition, fabricationof the equivalent device from the equivalent polymer tube is the same asthe fabrication of the device from the cooled polymer tube.

Certain embodiments may include expanding the polymer tube at atemperature below a T_(g) of the polymer. Other embodiments may includeexpanding the polymer tube in a temperature range greater than or equalto a T_(g) of the polymer and less than or equal to a T_(m) of thepolymer. Below T_(m), the polymer tube may retain its cylindrical shapeeven with applied pressure.

In certain embodiments, the radial expansion may be controlled to obtaina desired degree of induced molecular orientation, and hence, a desiredproperty of the implantable medical device. For example, the appliedpressure, temperature of the polymer tube, and the cooling rate of thepolymer tube may be controlled to obtain desired properties, such ascircumferential strength and/or modulus or rigidity, of the expandedpolymer tube.

FIGS. 8A and 8B illustrate a method of expanding a polymer tube for usein manufacturing an implantable medical device. FIG. 8A depicts an axialcross-section of a polymer tube 900 with an outside diameter 905positioned within an annular member 910. Annular member 910 may act as amold that limits the expansion of polymer tube 900 to a diameter 915,the inside diameter of annular member 910. Polymer tube 900 may beclosed at a distal end 920. Distal end 920 may be open in subsequentmanufacturing steps. A gas, such as air or an inert gas, may beconveyed, as indicated by an arrow 925, into an open proximal end 930 ofpolymer tube 900. Polymer tube 900 may be heated by heating the gas to atemperature above ambient temperature prior to conveying the gas intopolymer tube 900. Alternatively, heat may be applied to the exterior ofannular member 910. The conveyed gas combined with the applied heat mayact to radially expand polymer tube 900, as indicated by an arrow 935.FIG. 8B depicts polymer tube 900 in an expanded state with an outsidediameter 940 within annular member 910.

As discussed above, implantable medical devices may be fabricated fromtubes that are formed from planar polymer films or sheets. As usedherein, a “film” or “sheet” refers to something that is thin incomparison to its length and breadth.

In certain embodiments, a tube may be formed from a film by rolling afilm into a cylindrical shape. The sheet may then be bonded with asuitable adhesive. The film may be bonded at opposing edges of the filmthat are parallel or substantially parallel to a cylindrical axis. Thefilm may be cut so that the formed tube is a desired diameter.

It may be desirable to form a polymer tube from a polymer film that hasbiaxial orientation. Polymer films or sheets may be made by severaldifferent processes. A blown film or sheet can be made by expansion andstretching of a preform or parison. The preform or parison refers to ahollow molten tube extruded from the die head of a blow molding machineexpanded within the mold. In the blow molding process, air is blown intothe parison and it forms a bubble. The bubble is then drawn throughrollers, which stretch the film or sheet to the appropriate thickness.In another process, a polymer film may also be made by extrusion througha slit die, such as compression molding. In addition, cast film may bemade from a cast-film or chill-roll extrusion process. In a cast-filmprocess an extruded film or sheet is dimensionally stabilized bycontacting it with several chrome-plated chill rolls. Blown film hassome biaxial molecular orientation. Extruded film has extrusiondirection molecular orientation. However, cast film typically has verylittle molecular orientation.

Moreover, a polymer film with a desired degree of biaxial molecularorientation may be fabricated from blown, cast, or extruded film usingbiaxial stretching. Certain embodiments of a method of manufacturing animplantable medical device may include stretching a film along a firstaxis of stretching. In some embodiments, the method may further includestretching the film along a second axis of stretching. The film may bestretched by application of a tensile force or drawing tension. Thestretching of the film may induce molecular orientation in the polymerfilm, and hence high strength and modulus or rigidity, along the firstaxis of stretching and the second axis of stretching.

Certain embodiments may include fabricating an implantable medicaldevice from the stretched film. In one embodiment, fabricating animplantable medical device from the stretched film may include forming atube from the stretched film. Some embodiments of fabricating animplantable medical device from the stretched film may include forming apattern having at least one strut on at least a portion of the tube. Inanother embodiment, a pattern may be formed on the stretched film priorto forming a tube from the stretched sheet.

A mechanical property of the device may be more desirable than amechanical property of an equivalent device fabricated from anunstretched film. The dimensions of the device are equal to dimensionsof the equivalent device formed from an unstretched polymer film. Thefabrication of the equivalent device is the same as the fabrication ofthe device.

In certain embodiments, the stretching may be controlled to obtain adesired degree of induced molecular orientation, and hence, desiredproperties of the implantable medical device. The stretching may becontrolled by controlling various process parameters such as tensileforce used for stretching, the relative values of the tensile forceapplied along the axes, and the temperature of the film duringstretching.

In one embodiment, a polymer film may be stretched using a tenter. In atenter, stretching is performed inside of a box that may betemperature-controlled. Inside of the box, a film is grasped on eitherside by tenterhooks that exert a tensile force or drawing tension alongat least one axis. The degree of stretching along the axes may besubstantially equal, or alternatively, unbalanced. Therefore, themechanical properties of a polymer tube formed from a stretched film maybe controlled by the degree of stretching along each axis and also bythe relative amount stretching along the axes.

In certain embodiments, a tube may be formed to have a desired relativeorientation of a cylindrical axis of the tube with at least onestretching axis. A cylindrical axis of a tube formed from the stretchedsheet may be parallel, perpendicular, or at an angle between paralleland perpendicular to the first axis of stretching and/or the second axisof stretching. FIG. 9 depicts an x-y coordinate plane 942 forillustrating the relationship between an axis of stretching 944 and acylindrical axis 946 of a tube formed from a stretched sheet. An angle948 is the relative orientation between axis of stretching 944 andcylindrical axis 946.

It is believed that the maximum improvement in mechanical propertiessuch as strength due to stretching or deformation for a polymer isparallel to an axis of stretching or deformation. Therefore, a tube withits cylindrical axis perpendicular to a stretching axis may providemaximum circumferential strength of a tube, and hence, a devicemanufacturing from the tube. FIG. 10A illustrates a polymer film 950that has been stretched along two axes indicated by arrows 955 and 960to have biaxial molecular orientation. FIG. 10B depicts a polymer tube975 formed from polymer film 950. Polymer tube 975 is formed so that theaxes depicted by arrows 955 and 960 in FIG. 10A are along the radialdirection and cylindrical axis of polymer tube 975, respectively.

In some embodiments, the film may be stretched plastically beyond theyield point or elastic limit of the polymer along the first axis ofstretching and/or the second axis of stretching. However, it may bedesirable to stretch with a force that applies a stress that is lessthan an ultimate stress of the polymer to inhibit or prevent damage tothe film.

Alternatively, the polymer tube may be stretched elastically. Afterstretching, an elastically stretched film may be cooled relativelyquickly to inhibit contraction and dissipation of induced molecularorientation. For example, the stretched film may be cooled at atemperature substantially below an ambient temperature.

In one embodiment, a polymer film may be stretched at a temperaturegreater than or equal to a T_(g) and less than or equal to a T_(m) ofthe polymer. Below a T_(m), a planar polymer film may retain its shapeeven with applied tensile force or tension. In another embodiment, thefilm may be stretched at a temperature less than or equal to a T_(g) ofthe polymer. Additionally, the temperature of the film may be controlledto obtain desired properties, such as circumferential strength and/ormodulus or rigidity, of a polymer tube formed from the stretched film.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

1. A method of manufacturing a stent, comprising: introducing a polymerinto a forming apparatus comprising a first annular member disposedwithin a second annular member, wherein the polymer is conveyed throughan annular chamber as an annular film between the annular members;inducing circumferential flow in the annular film; forming a tube fromthe annular film; and fabricating a scaffold comprising a plurality ofinterconnecting struts from the tube.
 2. The method of claim 1, whereinthe polymer comprises a bioabsorbable polymer.
 3. The method of claim 1,wherein the introduced polymer is at a temperature above a meltingtemperature of the polymer.
 4. The method of claim 1, wherein theintroduced polymer is at a temperature below a melting temperature ofthe polymer, and wherein the forming apparatus is configured to melt thepolymer.
 5. The method of claim 1, wherein the polymer is introduced ina mixture comprising the polymer and a solvent.
 6. The method of claim1, wherein the annular film is at a temperature above a meltingtemperature of the polymer.
 7. The method of claim 1, wherein theforming apparatus comprises an extruder.
 8. The method of claim 1,wherein the circumferential flow is induced in the annular film byrotating the first annular member and/or rotating the second annularmember.
 9. The method of claim 8, wherein the circumferential flow isinduced in the annular film by a spiral channel on at least a portion ofa surface of the rotating first annular member.
 10. The method of claim8, wherein the circumferential flow is induced in the annular film by aspiral channel on at least a portion of a surface of the rotating secondannular member.
 11. The method of claim 1, wherein the circumferentialflow is induced in the annular film with at least a portion of theannular film external to the apparatus positioned over or within a thirdannular member that is configured to rotate at least a portion of theannular film.
 12. The method of claim 1, wherein the circumferentialflow is induced in the annular film by rotating the tube.
 13. The methodof claim 12, wherein the tube is rotated by positioning the tube over orwithin a third annular member that is configured to rotate the tube. 14.The method of claim 1, wherein the circumferential flow is induced inthe annular film external to the apparatus with at least a portion ofthe first annular member that is external to the apparatus.
 15. Themethod of claim 14, wherein rotation of the first annular member inducescircumferential flow to at least a portion of the annular film externalto the apparatus.
 16. The method of claim 1, further comprising drawingthe annular film to a desired diameter prior to cooling the annularfilm.
 17. The method of claim 1, further comprising cooling the annularfilm at or near an ambient temperature.
 18. The method of claim 1,further comprising cooling the annular film below an ambienttemperature.
 19. A method of manufacturing a stent, comprising:introducing a polymer into a forming apparatus comprising a firstannular member disposed within a second annular member, wherein thepolymer is conveyed through an annular chamber as an annular filmbetween the annular members; inducing spiral circumferential molecularorientation in the annular polymer film with a spiral channel on atleast a portion of a surface of the first annular member or the secondannular member; forming a tube from the annular film; and fabricating ascaffold comprising a plurality of interconnecting struts from the tube.20. The method of claim 19, wherein the first annular member and/or thesecond annular member rotate.